Lung carcinoma with ALK rearrangement

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Micrograph showing ALK positive lung adenocarcinoma. H&E stain.

Lung carcinoma with ALK rearrangement is subset of lung adenocarcinoma.

General

ALK (anaplastic lymphoma (receptor tyrosine) kinase):

  • Approximately 1-5% non-small cell lung carcinoma.[1]
    • Typically seen in nonsmokers and younger age patients.
    • Can be treated with crizotinib.[2]
      • Resistance to ALK inhibitors may occur due mutations in kinase domain.
      • Ceritinib is indicated for tumor with acquired resistance to crizotinib.[3]
  • Testing in FFPE tissue requires ~100 cells.[4]

Microscopic

Features:[1]

  • Adenocarcinoma - at least focally.
  • Solid signet-ring cell pattern - common.
  • Mucinous cribriform pattern - common.

DDx:

Images

www

IHC

Features:[1]

Images

Molecular

  • EML4-ALK fusion -- inv(2)(p21p23).[7]
    • C-terminus of ALK protein fuses with N-terminus portion of partner protein.
      • ALK fusion leads to ligand-independent constitutive activation of important pathways in oncogenesis and tumor progression.

Notes:

See also

References

  1. 1.0 1.1 1.2 Yoshida, A.; Tsuta, K.; Nakamura, H.; Kohno, T.; Takahashi, F.; Asamura, H.; Sekine, I.; Fukayama, M. et al. (Aug 2011). "Comprehensive histologic analysis of ALK-rearranged lung carcinomas.". Am J Surg Pathol 35 (8): 1226-34. doi:10.1097/PAS.0b013e3182233e06. PMID 21753699.
  2. Crystal, AS.; Shaw, AT. (Mar 2011). "New targets in advanced NSCLC: EML4-ALK.". Clin Adv Hematol Oncol 9 (3): 207-14. PMID 21475126.
  3. Shaw, AT.; Kim, DW.; Mehra, R.; Tan, DS.; Felip, E.; Chow, LQ.; Camidge, DR.; Vansteenkiste, J. et al. (Mar 2014). "Ceritinib in ALK-rearranged non-small-cell lung cancer.". N Engl J Med 370 (13): 1189-97. doi:10.1056/NEJMoa1311107. PMID 24670165.
  4. Popper, HH.; Tímár, J.; Ryska, A.; Olszewski, W. (Oct 2014). "Minimal requirements for the molecular testing of lung cancer.". Transl Lung Cancer Res 3 (5): 301-4. doi:10.3978/j.issn.2218-6751.2014.10.02. PMID 25806315.
  5. Lopes, LF.; Bacchi, CE. (Jul 2012). "Anaplastic lymphoma kinase gene rearrangement in non-small-cell lung cancer in a Brazilian population.". Clinics (Sao Paulo) 67 (7): 845-7. PMID 22892933.
  6. Takamochi, K.; Takeuchi, K.; Hayashi, T.; Oh, S.; Suzuki, K. (2013). "A rational diagnostic algorithm for the identification of ALK rearrangement in lung cancer: a comprehensive study of surgically treated Japanese patients.". PLoS One 8 (8): e69794. doi:10.1371/journal.pone.0069794. PMID 23936355.
  7. Li, Y.; Ye, X.; Liu, J.; Zha, J.; Pei, L. (Jan 2011). "Evaluation of EML4-ALK fusion proteins in non-small cell lung cancer using small molecule inhibitors.". Neoplasia 13 (1): 1-11. PMID 21245935.
  8. 8.0 8.1 Gainor, JF.; Varghese, AM.; Ou, SH.; Kabraji, S.; Awad, MM.; Katayama, R.; Pawlak, A.; Mino-Kenudson, M. et al. (Aug 2013). "ALK rearrangements are mutually exclusive with mutations in EGFR or KRAS: an analysis of 1,683 patients with non-small cell lung cancer.". Clin Cancer Res 19 (15): 4273-81. doi:10.1158/1078-0432.CCR-13-0318. PMID 23729361.